Circulating metabolic signatures of rapid and slow progression to type 1 diabetes in islet autoantibody-positive children
Lamichhane, Santosh; Sen, Partho; Dickens, Alex M.; Kråkström, Matilda; Ilonen, Jorma; Lempainen, Johanna; Hyöty, Heikki; Lahesmaa, Riitta; Veijola, Riitta; Toppari, Jorma; Hyötyläinen, Tuulia; Knip, Mikael; Orešič, Matej (2023-09-06)
Lamichhane S, Sen P, Dickens AM, Kråkström M, Ilonen J, Lempainen J, Hyöty H, Lahesmaa R, Veijola R, Toppari J, Hyötyläinen T, Knip M and Orešič M (2023) Circulating metabolic signatures of rapid and slow progression to type 1 diabetes in islet autoantibody-positive children. Front. Endocrinol. 14:1211015. doi: 10.3389/fendo.2023.1211015
© 2023 Lamichhane, Sen, Dickens, Kråkström, Ilonen, Lempainen, Hyöty, Lahesmaa, Veijola, Toppari, Hyötyläinen, Knip and Orešič. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe20231016140277
Tiivistelmä
Abstract
Aims/hypothesis: Appearance of multiple islet cell autoantibodies in early life is indicative of future progression to overt type 1 diabetes, however, at varying rates. Here, we aimed to study whether distinct metabolic patterns could be identified in rapid progressors (RP, disease manifestation within 18 months after the initial seroconversion to autoantibody positivity) vs. slow progressors (SP, disease manifestation at 60 months or later from the appearance of the first autoantibody).
Methods: Longitudinal samples were collected from RP (n=25) and SP (n=41) groups at the ages of 3, 6, 12, 18, 24, or ≥ 36 months. We performed a comprehensive metabolomics study, analyzing both polar metabolites and lipids. The sample series included a total of 239 samples for lipidomics and 213 for polar metabolites.
Results: We observed that metabolites mediated by gut microbiome, such as those involved in tryptophan metabolism, were the main discriminators between RP and SP. The study identified specific circulating molecules and pathways, including amino acid (threonine), sugar derivatives (hexose), and quinic acid that may define rapid vs. slow progression to type 1 diabetes. However, the circulating lipidome did not appear to play a major role in differentiating between RP and SP.
Conclusion/interpretation: Our study suggests that a distinct metabolic profile is linked with the type 1 diabetes progression. The identification of specific metabolites and pathways that differentiate RP from SP may have implications for early intervention strategies to delay the development of type 1 diabetes.
Kokoelmat
- Avoin saatavuus [42543]
